Complex Formation between Heptakis(2,6-di-O-methyl)-β-cyclodextrin and Cyclopentadienyl Molybdenum(II) Dicarbonyl Complexes: Structural Studies and Cytotoxicity Evaluations

Abstract

The inclusion compounds isolated from nonaqueous solutions of heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB) and the complexes [CpMoL2(CO)2](BF4) (L = MeCN, L2 = 2,2′-biimidazole) were characterized in the solid state by powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), 13C{1H} CP/MAS NMR, and FTIR spectroscopy. Powder XRD showed that the compound with [CpMo(MeCN)2(CO)2](BF4) was amorphous, while that with [CpMo(H2biim)(CO)2](BF4) was microcrystalline. The powder XRD pattern of the microcrystalline product could be satisfactorily indexed in the orthorhombic crystal system with space group P212121 and final unit cell parameters of a = 28.489(3) Å, b = 19.198(2) Å, and c = 16.042(2) Å. A hypothetical structural model for the crystal packing was obtained through Monte Carlo optimizations using fixed DIMEB, [CpMo(H2biim)(CO)2]+, and BF4− geometries. In the final model the BF4− anions are housed inside the toroidal cavity of DIMEB and the organometallic complex cations are regularly distributed in between the DIMEB-tetrafluoroborate complexes, occupying the intermolecular void spaces. The cytotoxicity of the free complexes and the corresponding DIMEB adducts was tested against K1735-M2 mouse melanoma cells and H9c2 rat myoblast cells in aqueous solution. The MeCN complex and its corresponding DIMEB adduct showed no significant activity for use as chemotherapeutic agents. In contrast, the biimidazole complex exhibited significant cytotoxicity against K1735-M2 cells, especially for concentrations above 50 μM, and the cytotoxicity was even higher when the DIMEB adduct was used. Epifluorescence microscopy indicated that mitochondrial alterations took place at an earlier time point than major changes in cell morphology.